Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation

Colorectal Cancer (CRC) Clinical Trial

— CodeBreak300  

Official title:

A Phase 3 Multicenter, Randomized, Open-label, Active-controlled Study of Sotorasib and Panitumumab Versus Investigator's Choice (Trifluridine and Tipiracil, or Regorafenib) for the Treatment of Previously Treated Metastatic Colorectal Cancer Subjects With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05198934
• Other study ID #: 20190172
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 19, 2022
• Est. completion date: March 12, 2025

Study information

• Verified date: May 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to compare progression-free survival (PFS) in previously treated participants with Kirsten rat sarcoma (KRAS) p.G12C mutated colorectal cancer (CRC) receiving sotorasib 240 mg once daily (QD) and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib), and sotorasib 960 mg QD and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: March 12, 2025
• Est. primary completion date: March 12, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures.

• Age =18 years.

• Pathologically documented metastatic colorectal adenocarcinoma with Kirsten rat sarcoma (KRAS) p.G12C mutation as determined by prospective central testing, using the analytically validated Qiagen Therascreen KRAS RGQ polymerase chain reaction Kit in CRC as an investigational device demonstrating a KRAS p.G12C mutation is present. Local testing and documentation of KRAS p.G12C mutation should have been previously performed as part of standard of care.

• Participants will have received at least 1 prior line of therapy for metastatic disease. Participants must have received and progressed or experienced disease recurrence on or after fluoropyrimidine, irinotecan, and oxaliplatin given for metastatic disease unless the participant, in the opinion of the investigator, is not a candidate for fluoropyrimidine, irinotecan, or oxaliplatin, in which case, the participant may be eligible after investigator discussion with Amgen medical monitor provided participant has received at least one prior line of therapy for metastatic disease and provided trifluridine and tipiracil or regorafenib is deemed the appropriate next line of therapy for the participant.

• Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Lesions previously radiated are not considered measurable unless they have progressed after radiation.

• Eastern Cooperative Oncology Group (ECOG) Performance Status of =2.

• Life expectancy of >3 months, in the opinion of the investigator.

• Adequate hematologic and end-organ function, defined as the following within 2 weeks prior to cycle 1 day 1:

• Absolute neutrophil count (ANC) =1.5 x 10^9/L (without granulocyte colony stimulating factor support within 2 weeks of laboratory test used to determine eligibility).

• Hemoglobin =9.0 g/dL (without transfusion within 2 weeks of laboratory test used to determine eligibility).

• Platelet count =100 x 10^9/L (without transfusion within 2 weeks of laboratory test used to determine eligibility).

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 times the upper limit of normal (ULN).

• Serum bilirubin =1.0 x ULN. For participants with Gilbert's disease, total bilirubin or direct bilirubin needs to be =1.0 x ULN.

• International normalized ratio (INR) and activated partial thromboplastin time (or partial thromboplastin time) =1.5 x ULN. Prothrombin time (PT) =1.5 x ULN may be used instead of INR for sites whose labs do not report INR.

• Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation =30 mL/min/1.73 m^2.

• Fridericia's Correction Formula (QTcF) =470 msec.

Exclusion Criteria:

• Active brain metastases. Participants who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria: a) residual neurological symptoms grade =2; b) on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and c) follow-up magnetic resonance imaging (MRI) performed within 28 days of day 1 shows no progression or new lesions appearing.

• History or presence of hematological malignancies unless curatively treated with no evidence of disease =2 years.

• History of other malignancy within the past 3 years, with the following exceptions:

• Malignancy treated with curative intent and with no known active disease present for =3 years before enrollment and felt to be at low risk for recurrence by the treating physician.

• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.

• Adequately treated cervical carcinoma in situ without evidence of disease.

• Adequately treated breast ductal carcinoma in situ without evidence of disease.

• Prostatic intraepithelial neoplasia without evidence of prostate cancer.

• Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ.

• Leptomeningeal disease.

• Significant gastrointestinal (GI) disorder that results in significant malabsorption, requirement for intravenous (IV) alimentation, or inability to take oral medication.

• History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis.

• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to randomization, unstable arrhythmias or unstable angina.

• Previous treatment with a KRAS G12C inhibitor.

Related Conditions & MeSH terms

• Colorectal Cancer (CRC)
• Colorectal Neoplasms
• Sarcoma

Intervention

Drug:
• Sotorasib
Sotorasib will be administered orally
• Panitumumab
Panitumumab will be administered as intravenous (IV) infusion
• Trifluridine and Tipiracil
Trifluridine and Tipiracil will be administered orally
• Regorafenib
Regorafenib will be administered orally

Locations

Country	Name	City	State
Australia	Chris OBrien Lifehouse	Camperdown	New South Wales
Australia	GenesisCare -North Shore (Oncology)	St Leonards	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
France	Centre Hospitalier Universitaire de Lyon - Hopital Edouard Herriot	Lyon Cédex 3
France	Institut regional du Cancer Montpellier	Montpellier Cedex 5
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital Haut -lévêque	Pessac
Germany	Charite Universitaetsmedizin Berlin, Charité Campus Virchow-Klinikum	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden	Dresden
Germany	Universitaetsmedizin Goettingen - Georg-August-Universitaet	Goettingen
Germany	Klinikum der Universitaet Muenchen Campus Grosshadern	Muenchen
Germany	Universitaetsklinikum der Eberhard Karls Universitaet Tuebingen	Tuebingen
Greece	Evgenidio Hospital I Agia Trias	Athens
Greece	General Hospital of Athens Laiko	Athens
Greece	Hygeia Hospital	Athens
Greece	University Hospital of Heraklion	Heraklion - Crete
Greece	University Hospital of Patras	Patra
Greece	Agios Loukas Clinic	Thessaloniki
Greece	Theagenion Anticancer Hospital	Thessaloniki
Italy	Istituto Ospedaliero Fondazione Poliambulanza	Brescia
Italy	Azienda Ospedaliera Rilievo Nazionale e Alta Specializzazione Garibaldi Nesima	Catania
Italy	Azienda Ospedaliera Santa Croce e Carle	Confreria (CN)
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Ospedale Policlinico San Martino IRCCS	Genova
Italy	Azienda Sanitaria Locale 5 Spezzino Ospedale S Andrea	La Spezia
Italy	Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II	Lecce
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Azienda Ospedaliero Universitaria di Cagliari Policlinico Duilio Casula	Monserrato CA
Italy	Azienda Ospedaliero Universitaria Luigi Vanvitelli	Napoli
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale	Napoli
Italy	Azienda Ospedaliero Universitaria Maggiore della Carita	Novara
Italy	Istituto Oncologico Veneto IRCCS	Padova
Italy	Azienda Ospedaliera Universitaria Pisana Ospedale Santa Chiara	Pisa
Italy	Azienda Ospedaliera San Carlo	Potenza
Italy	Azienda Unita Sanitaria Locale di Reggio Emilia Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Azienda Ospedaliera San Giovanni Addolorata	Roma
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	Fondazione Policlinico Tor Vergata	Roma (RM)
Italy	Azienda Ospedaliera Cardinale Giovanni Panico	Tricase
Italy	Azienda Unita Locale Socio Sanitaria Berica 8	Vicenza
Japan	Hyogo Cancer Center	Akashi-shi	Hyogo
Japan	Chiba Cancer Center	Chiba-shi	Chiba
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba
Japan	St Marianna University Hospital	Kawasaki-shi	Kanagawa
Japan	Saitama Cancer Center	Kitaadachi-gun	Saitama
Japan	The Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto-ku	Tokyo
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama-shi	Ehime
Japan	Aichi Medical University Hospital	Nagakute-shi	Aichi
Japan	National Hospital Organization Osaka National Hospital	Osaka-shi	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Osaka University Hospital	Suita-shi	Osaka
Japan	Shizuoka Cancer Center	Sunto-gun	Shizuoka
Japan	Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center	Yokohama-shi	Kanagawa
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Mexico	Superare Centro de Infusion SA de CV	Ciudad de Mexico	Distrito Federal
Mexico	Trials In Medicine SC	Ciudad de Mexico
Mexico	Health Pharma Professional Research SA de CV	Mexico City	Distrito Federal
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Cataluña
Spain	Hospital Universitari Vall d Hebron	Barcelona	Cataluña
Spain	Hospital Universitario Reina Sofia	Cordoba	Andalucía
Spain	Hospital General Universitario de Elche	Elche	Comunidad Valenciana
Spain	Hospital Universitario Virgen de las Nieves	Granada	Andalucía
Spain	Hospital Universitario La Paz	Madrid
Spain	Complexo Hospitalario Universitario de Ourense	Ourense	Galicia
Spain	Hospital Universitario de Navarra	Pamplona	Navarra
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Spain	Hospital General Universitario de Valencia	Valencia	Comunidad Valenciana
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation	Taoyuan
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Royal Free Hospital	London
United Kingdom	Royal Marsden Hospital	London
United Kingdom	Maidstone Hospital	Maidstone
United Kingdom	Mount Vernon Cancer Centre	Northwood
United Kingdom	Royal Marsden Hospital	Sutton
United States	University of Michigan	Ann Arbor	Michigan
United States	Central Alabama Research	Birmingham	Alabama
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	City of Hope National Medical Center	Duarte	California
United States	Revive Research Institute	Farmington Hills	Michigan
United States	Moses H Cone Memorial Hospital	Greensboro	North Carolina
United States	Best Cancer Care & Hematology	Houston	Texas
United States	Kelsey Research Foundation	Houston	Texas
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Lumi Research	Kingwood	Texas
United States	Lancaster General Hospital Ann B Barshinger Cancer Institute	Lancaster	Pennsylvania
United States	Sparrow Clinical Research Institute	Lansing	Michigan
United States	Northwest Georgia Oncology Centers PC	Marietta	Georgia
United States	Lakes Research LLC	Miami Lakes	Florida
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	University of California Irvine	Orange	California
United States	Revive Research Institute	Sterling Heights	Michigan
United States	Upstate University Hospital	Syracuse	New York
United States	Johns Hopkins University School of Medicine	Washington	District of Columbia
United States	White Plains Hospital Center for Cancer Care	White Plains	New York

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Mexico,  Spain,  Taiwan,  United Kingdom, 

References & Publications (1)

Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, Karamouzis MV, Ruiz-Garcia E, Kim TW, Kuboki Y, Meriggi F, Cunningham D, Yeh KH, Chan E, Chao J, Saportas Y, Tran Q, Cremolini C, Pietrantonio F. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Dec 7;389(23):2125-2139. doi: 10.1056/NEJMoa2308795. Epub 2023 Oct 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)		Approximately 3 years
Secondary	Overall Survival (OS)		Approximately 3 years
Secondary	Objective Response Rate (ORR)		Approximately 3 years
Secondary	Duration of Response (DOR)		Approximately 3 years
Secondary	Time to Response (TTR)		Approximately 3 years
Secondary	Disease Control Rate (DCR)		Approximately 3 years
Secondary	Investigator Assessed ORR		Approximately 3 years
Secondary	Investigator Assessed PFS		Approximately 3 years
Secondary	Number of Participants with a Treatment-emergent Adverse Event (TEAE)	A TEAE is any untoward medical occurrence in a clinical study participant following first dose of treatment irrespective of a causal relationship with the study treatment. Any clinically significant changes in vital signs and clinical laboratory tests following first dose will be recorded as TEAEs.	Approximately 3 years
Secondary	Change from Baseline in Fatigue Severity as Measured by Item 3 of the Brief Fatigue Inventory (BFI)	Item 3 of the BFI records a participants' fatigue on a scale from 0 to 10. Higher scores indicate a higher severity of fatigue. An increase in score from baseline indicates a worsening of fatigue. A decrease in score from baseline indicates an improvement in fatigue.	Baseline and Week 8
Secondary	Change from Baseline in Pain Severity as Measured by Item 3 of the Brief Pain Inventory (BPI)	Item 3 of the BPI records a participants' pain on a scale from 1 to 10, where pain is mild (score of 1 to 4), moderate (score of 5 to 6), or severe (score of 7 to 10). An increase in score from baseline indicates a worsening of pain. A decrease in score from baseline indicates a lessening of pain.	Baseline and Week 8
Secondary	Change from Baseline in Physical Functioning as Measured by the Physical Function Domain of the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30)	The physical function domain of the EORTC QLQ-C30 assesses a participants' quality of life regarding their physical function on a scale from 1 to 4, with higher scores indicating a worse outcome. An increase in score from baseline indicates a worsening of physical functioning. A decrease in score from baseline indicates an improvement in physical functioning.	Baseline and Week 8
Secondary	Change from Baseline in Global Health Status as Measured by Questions 29 and 30 of the EORTC QLQ-C30	Questions 29 and 30 of the EORTC QLQ-C30 assess a participants' global health status on a scale from 1 to 7, with higher scores indicating a better outcome. An increase in score from baseline indicates an improvement in global health status. A decrease in score from baseline indicates a worsening in global health status.	Baseline and Week 8
Secondary	Change from Baseline For All Subscales of the BFI	The BFI is a questionnaire that includes 3 items to assess fatigue severity and 5 items to assess interference due to fatigue, with each item reported on a numeric rating scale from 0 to 10. Higher scores indicate a higher severity of fatigue. An increase in score from baseline indicates a worsening of fatigue. A decrease in score from baseline indicates an improvement in fatigue.	Baseline and Week 8
Secondary	Change from Baseline For All Subscales of the BPI	The BPI is a 9-item questionnaire which includes 2 body diagrams, four items to assess pain severity, four items to assess pain interference and one question about percentage of pain relief by analgesics. The level of pain and pain interference assessed can be divided into categories based on score of mild (1 to 4), moderate (5 to 6), and severe (7 to 10). An increase in score from baseline indicates a worsening of pain. A decrease in score from baseline indicates a lessening of pain.	Baseline and Week 8
Secondary	Change from Baseline For All Subscales and Domains of EORTC QLQ-C30	The EORTC QLQ-C30 is a self-reporting 30-item generic instrument which assesses 5 functional domains (physical, role, emotional, cognitive, social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties), and a global health status/quality of life (QOL) scale. Higher scores indicate a worse outcome. An increase in score from baseline indicates a worsening of outcome. A decrease in score from baseline indicates an improvement in outcome.	Baseline and Week 8
Secondary	Change from Baseline in Visual Analog Scale (VAS) Scores as Measured by EuroQol-5D level 5 (EQ-5D-5L)	The EQ-5D-5L questionnaire is a 2-page, standardized instrument for use as a measure of health outcome. It is comprised of a 5-dimension health status measure and a visual analogue scale. The 5-dimension health status measure evaluates: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on a 5-level scale: no problems, slight problems, moderate problems, severe problems, and extreme problems. The visual analogue scale records the participant's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'.	Baseline and Week 8
Secondary	Average Score on Single Question on Symptom Bother GP5 from Functional Assessment of Cancer Therapy - General (FACT-G)	The GP5 from the FACT-G is a single item included in the Physical Well-Being subscale of the FACT-G. Responses to the item: "I am bothered by side effects of treatment" are rated on a 5-point Likert scale from "not at all" to "very much".	Approximately 2 years
Secondary	Average Score of Patient Global Impression of Change (PGIC)	The PGIC scale consists of one item which measures the participants' perception of change in their condition relative to the beginning of the study. Responses are rated on a 7-item response scale ranging from very much improved to very much worse.	Approximately 2 years
Secondary	Maximum Plasma Concentration (Cmax) of Sotorasib		Day 1 to approximately 2 years
Secondary	Cmax of Panitumumab		Day 1 to approximately 2 years
Secondary	Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib		Day 1 to approximately 2 years
Secondary	AUC of Panitumumab		Day 1 to approximately 2 years

External Links

•   AmgenTrials clinical trials website